JP2007505863A - Composition comprising a soluble calcium sequestering agent - Google Patents

Abstract

A dentifrice composition is disclosed comprising a soluble calcium sequestering agent that is not an oxidizing agent, wherein the composition has an RDA value of below 30 and an IVSR value greater than 50 (when compared to a Control) and an orally acceptable vehicle, wherein the calcium sequestering agent is present in a proportion of 1-20 wt % and an abrasive is present in a proportion of 0-5 wt % of the composition. The composition is highly effective in removing stains from natural teeth and prosthetics and will not damage the tooth or prosthetic due to excessive abrasion.

Description

  The present invention relates to a dentifrice composition for cleaning natural teeth and dentures, in particular a composition comprising a fluoride source and a soluble calcium sequestering agent that is not an oxidizing agent. Such a composition exhibits low abrasiveness as well as excellent cleaning properties.

  Dentifrices have been used for over 2,000 years, but the main purpose of dentifrices is to remove surface deposits from the teeth. Removal of surface deposits from the teeth can be accomplished using either chemical or mechanical cleaners. Examples of chemical cleaning agents include calcium-metal sequestering agents, such as polyphosphates (eg, tripolyphosphate), and mechanical cleaning agents include abrasives such as precipitated silica or calcium carbonate. Is mentioned. One example of a polishing cleaner is amorphous hydrated silica. Further, in order to decolorize the dirt on the teeth, the dentifrice may contain a bleaching agent. However, this does not effectively remove dirt, and effective bleaching agents can damage oral tissues and are difficult to formulate properly. Hydrogen peroxide is a well-known bleaching agent, but in the case of dentifrices containing peroxide, the lifetime of peroxide in the oral cavity is very short. Human plaque contains a significant level of the peroxide-degrading enzyme catalase, which is extremely capable of maintaining an effective level of peroxide on the tooth surface for a time sufficient to bleach the soil. Means difficult. The use of more damaging bleach than peroxide raises concerns about tissue damage.

  Traditional dentifrice formulations contain a number of specific ingredients such as abrasives, humectants, fluoride sources, binders, anti-plaque agents, dyes, flavoring agents, preservatives, water and other optional ingredients. Fluoride is an important adjunct for oral health, especially dental enamel health. Effective removal of surface-fouling stains from teeth or dentures is usually associated with a substantially abrasive formulation. However, dentifrice compositions containing abrasives can damage the surface of the teeth as well as the surface of the denture, so that the dentifrice preparation does not cause excessive polishing on the teeth or dentures and provides effective cleaning. It is recognized that achieving is extremely important.

  WO-A-95 / 17158 reduces or eliminates surface-fouling from natural teeth or dentures, including dentally acceptable formulations containing 5-15% by weight water-soluble alkali metal tripolyphosphate A composition is described and claimed. All examples of dentifrice formulations described in WO-A-95 / 17158 contain a normal tooth abrasive, for example abrasive silica, and are disclosed to contain in the range of 5 to 80% by weight.

An established method for determining the abrasiveness of dentifrice formulations is by measuring the target dentin abrasivity (RDA) (Hefferen, JJ. A laboratory method for measuring dentifrice abrasivity. J. Dent. Res 55 563-573, 1976). In this assay, dentin wear due to prolonged brushing using a 25:40 w / w slurry test toothpaste is measured from prepared human dentin samples. Irradiating a dentin sample produces ³² P in the mineral. In this assay, the radioactivity in the supernatant after brushing is measured against that released by brushing with a standard slurry of calcium pyrophosphate.

  Cleaning performance is closely related to soil removal and can be measured in various ways. A very useful in vitro soil removal (IVSR) assay (Layer TM, McConville PS and Wicks MA. Stain removal efficacy of whitening toothpastes-in vitro studies. J. Dent. Res. 79: 216 abstract 581, 2000) Used in the present invention. This assay aims to maximize the relevance of the assay to the in vivo situation by using untreated naturally soiled bovine teeth as a substrate. Test teeth with a toothbrush for a long time with a 1: 3 slurry of test toothpaste with water. Quantify soil removal using a color luminance meter. A control dentifrice formulation containing 14% Zeodent 113 ™ abrasive silica in a conventional substrate containing water, sorbitol, glycerin, PEG, flavor, SLS, sodium saccharin, xantham gum and sodium fluoride (available from JM Huber Corporation ) And the performance may be measured. IVSR is also known as the natural exogenous soil removal assay, or NESR, and is so called in several publications.

  Therefore, the cleaning efficiency can be expressed as the ratio of IVSR and RDA.

  The IVSR values quoted herein are relative to the control formulation assigned an arbitrary value of 100.

EP 0 835 223B discloses amorphous silica having a low polishing value, and when this is contained in a dentifrice, excellent detergency is maintained. However, this document only considers abrasive silica as a cleaning material for the composition and describes amorphous silica in terms of its physical properties. Thus, EP 0 835 223B is between RDA value is 30 to 70, the oil absorption capacity is 100 to 155 cm ^3/100 g, amorphous, wherein the BET surface area is less 200 m ² / g Claim silica.

  From this document it is clear that many formulations whose cleaning properties depend on their abrasive content are described and claimed in terms of the physical properties of the abrasive. For example, EP-A-0 396 460 describes amorphous silica in terms of BET surface area, oil absorption, pore volume, pH, refractive index and translucency in Example 1.

  EP-A-0 002 184 discloses the use of finely granulated sodium polyphosphate for tooth cleaning alone or in combination with a commercial toothpaste formulation. Describes the polishing effect of sodium polyphosphate and how this material enhances tooth cleaning without damaging the tooth constituents.

  The prior art does not disclose or describe highly effective dentifrice formulations that do not contain traditional amounts of abrasive. The “extremely effective dentifrice preparation” means a dentifrice preparation that sufficiently removes dirt from natural teeth or dentures and at the same time does not damage dentin, enamel or dentures due to excessive abrasiveness.

  It is an object of the present invention to provide a dentifrice composition for natural teeth or dentures that solves one or more of the problems set forth above.

  Accordingly, the present invention is a dentifrice composition comprising a soluble calcium sequestering agent that is not an oxidizing agent, the composition comprising an RDA value of 30 or less and an IVSR value of 50 or more (when compared to a control) and Having an acceptable vehicle in the oral cavity, wherein the calcium sequestering agent is present in a proportion of 1-20% by weight of the composition, and the abrasive is present in a proportion of 0-5% by weight of the composition The above dentifrice composition is provided.

  Preferably, the composition is a non-gel toothpaste that is supplied in a collapsible container (eg, a tube or pump) from which it can be extruded and used on a toothbrush Fluid.

  Preferably, the RDA value is 25 or less, preferably 20 or less, and most preferably as low as possible so that the composition is substantially non-abrasive. Preferably, the IVSR value reaches 250, preferably 200 or more, more preferably 100 or more, for example, 75 to 150 (eg, 75 to 120).

The soluble calcium-metal sequestering agent may be a calcium chelator. Suitable soluble calcium sequestering agents include the following:
Formula: M ⁺ _{n + 2} [P _n O _{3n + 1} ]
(Where n> 1, M = alkali metal, hydrogen ion or ammonium ion)
Polyphosphate (also known as condensed phosphate). This includes the following: polyphosphates such as alkali metal salts of pyrophosphate, and pyrophosphate (in which case hydrogen ions and / or ammonium ions may be partially substituted for alkali metal ions) Good). Examples of these are:
Na ₄ P ₂ O ₇ Tetrasodium pyrophosphate
Na ₂ H ₂ P ₂ O ₇ Disodium dihydrogen pyrophosphate
K ₄ P ₂ O ₇ Tetrapotassium pyrophosphate
K ₂ H ₂ P ₂ O ₇ Dipotassium dihydrogen pyrophosphate
Na ₂ K ₂ P ₂ O ₇ Disodium dipotassium pyrophosphate tripolyphosphates, eg alkali and mixed alkali metal salts of polyphosphates, and tripolyphosphates (in which case alkali metal ions with hydrogen and / or ammonium ions May be partially substituted). Examples of these are:
Na ₅ P ₃ O ₁₀ pentasodium tripolyphosphate
K ₅ P ₃ O ₁₀ Tripotassium tripolyphosphate More advanced polyphosphates, such as sodium and potassium tetraphosphates, and hexametaphosphate (also known as “glassy phosphate” or “polypyrrolate”). Carboxylates such as alkali metal citrate (which may be partially substituted with hydrogen or ammonium ions), alkali metal acetate, lactate, tartrate and maleate (partially with hydrogen or ammonium ions) May be substituted). Alkali metal salts of ethylenediaminetetraacetic acid (EDTA) (which may be partially substituted with hydrogen ions or ammonium ions) and alkali metal salts of edtronic acid.

  Two or more calcium sequestering agents may be used in combination in the composition.

  A preferred soluble calcium-sequestering agent is pentasodium tripolyphosphate, often referred to as sodium tripolyphosphate.

  When high levels of soluble calcium-metal sequestering agents are used in formulations, there are often certain amounts of undissolved solids in the formulation. Even if there is an undissolved calcium-sequestering agent in the composition of the present invention, it dissolves rapidly during use and provides a cleaning effect in its dissolved state.

  A soluble calcium-metal sequestering agent such as sodium tripolyphosphate can be included in a proportion of 1 to 20%, preferably 2 to 15%, more preferably 5 to 15% by weight of the dentifrice composition. By using the calcium sequestering agent in the composition at a ratio lower than the solubility limit, it is possible to provide a gel or liquid composition in which the calcium sequestering agent is dissolved. It does not contain undissolved solid particles and can be a transparent gel or liquid.

  The composition can contain a fluoride ion source. Fluoride ions stabilize oral polyphosphates. In the case of a composition used for cleaning natural teeth, the inclusion of a fluoride ion source is desirable for its caries prevention activity, but in the case of a composition used for cleaning artificial dentures, such activity Is not necessary. The fluoride ion source is provided by an alkali metal fluoride, preferably sodium fluoride, alkali metal monofluorophosphate, stannous fluoride, and the like. However, the fluoride ion source is preferably an alkali metal fluoride, most preferably sodium fluoride. The fluoride ion source serves in a well-known manner for caries prevention. Preferably, the fluoride ion source is sufficient to provide a caries preventive effective amount and a phosphatase enzyme inhibitory amount, e.g., about 25 ppm to about 3,500 ppm, preferably about 1,100 ppm as fluoride ions. Use an appropriate amount. For example, the formulation contains 0.1-0.5% by weight alkali metal fluoride (such as sodium fluoride).

  Preferably the pH of the composition is 6 to 10.5, more preferably 7 to 9.5. Typically, the composition may contain up to 0.5% by weight sodium hydroxide to achieve a suitable pH.

  In the composition of the present invention, i.e., a composition that can be extruded onto a toothbrush, the oralally acceptable vehicle may generally comprise a conventional composition, including, for example, thickeners, binders and humectants. It is. Preferred binders include, for example, xanthan gum, carrageenan, alginates, cellulose ethers and esters. Preferred humectants include glycerin, sorbitol, propylene glycol and polyethylene glycol. A preferred humectant system consists of glycerin, sorbitol and polyethylene glycol. In addition, the vehicle acceptable to the oral cavity is optionally one or more surfactants, sweeteners, flavorings, caries preventives (other than fluoride ion sources), anti-plaque agents, antibacterial agents (eg, Triclosan or cetylpyridinium chloride), tooth perception desensitizing agents, colorants and pigments. Useful surfactants include water-soluble salts of alkyl sulfates containing 10 to 18 carbon atoms in the alkyl moiety, such as sodium lauryl sulfate, but other anionic surfactants, as well as nonions, zions, Cationic and amphoteric surfactants may be used.

  When using an aqueous oral acceptable vehicle, the toothpaste compositions of the present invention comprise about 10 to about 80% by weight of a humectant (eg, sorbitol, glycerin, polyethylene glycol or xylitol); By suitably including 5% by weight detergent; 0 to about 5% by weight sweeteners and flavors; and water and an effective amount of binding and thickening agents (eg, about 0.1 to about 15% by weight), The toothpaste of the present invention having the desired stability and fluidity is provided.

  It is preferable to use thickened silica as the thickener. So-called “thickened silica” is a well-known silica that provides a thickening action to the composition, although the polishing action is relatively small compared to known abrasive silicas such as Zeodent 113 ™. Suitable thickening silicas are well known, SYLOBLANC® by Huber under the trademark Zeodent (eg Zeodent 167) and Degussa AG under the trademark SIDENT 22S (eg SIDENT 22S®). (Example: SYLOBLANC 15 (registered trademark)) are commercially available. For example, the composition may comprise about 20% by weight, typically 5-15% by weight of thickened silica.

  The compositions of the present invention may comprise an abrasive material, such as the aforementioned toothpaste, for example, the well-known type of “abrasive silica” commonly used in Zeodent 113 ™. However, in order to achieve an RDA of 30 or less, this type of abrasive is preferably contained as little as possible, and other solid particles of the composition (for example, undissolved calcium sequestering agent or In addition to the mild polishing action caused by any thickening silica present, etc., it preferably contains 5 wt% or less, more preferably 2 wt% or less, most preferably 0 wt% abrasive. For the purposes of the present invention, an abrasive is defined as a material having an RDA of 30 or greater. If the RDA of the silica is 30 or less, a larger amount of silica may be included, which is a typical abrasive silica content level (for example, up to 25%) in toothpaste.

  With respect to the RDA values shown in the previous paragraph, it should be noted that the slurry conditions used to determine the RDA of the abrasive material are different from those used to determine the RDA of the formulated toothpaste. The raw slurry conditions are 10 g abrasive in 10% glycerin and 50 ml 0.5% carboxymethylcellulose slurry, while the formulated toothpaste slurry conditions are 25 g toothpaste and 40 ml water. . Therefore, care must be taken when comparing the RDA value for abrasives as raw materials with the RDA value for fully formulated toothpaste.

  Accordingly, a preferred dentifrice composition of the present invention comprises a soluble calcium sequestering agent that is not an oxidizing agent, which composition has an RDA value of 30 or less and an IVSR value of 50 or more (when compared to the control) and oral cavity. Having an acceptable vehicle, wherein the calcium sequestering agent is present in a proportion of 1-20% by weight of the composition, preferably 5-10% by weight, 0-5% by weight, preferably 0 Contains a weight percent abrasive, typically abrasive silica.

  The dentifrice composition may be in the form of either a single or a two-phase composition.

  The composition is preferably in the form of a normal toothpaste type composition that can be squeezed out of a collapsible tube. It is also suitable for dispensing from pressurized aerosol containers.

  The toothpaste type composition of the present invention comprises a calcium sequestering agent and fluoride source (if present) and an oral-acceptable dental vehicle (which may be anhydrous, but preferably aqueous) according to conventional methods. Can be prepared by mixing a dental vehicle that is acceptable to the oral cavity to form a storage stable semi-solid extrudable material useful as a dentifrice.

The compositions of the present invention are described below, but this is only a non-limiting example.

  Various embodiments of the invention can be prepared.

  Example 1 is a formulation in which the calcium-sequestering chemical cleaning system is sodium tripolyphosphate (STP). It can be seen that as the thickening silica increases, the solids level in the formulation decreases. Other polyphosphates may be used as chemical cleaning agents and / or caries prevention agents.

  Example 2 is an equivalent formulation using mixed pyrophosphate instead of STP. By adding sodium hydroxide to raise the pH, the stability of the polyphosphate component is enhanced.

  Example 3 uses trimetaphosphate and Example 4 uses sodium hexametaphosphate.

  Example 5 shows that a mixed calcium-metal ion sequestration system can be used. This example combines various polyphosphates.

Example 6 uses an effective amount of polycarboxylate, ie trisodium citrate, as a calcium-sequestering agent.

  From Example 7, it is clear that there is no need to increase the thickened silica to make up for the lack of polished silica. In this example, the level of thickened silica is the same as the formulation with a standard level of abrasive (6.5%). However, moderate viscosity is maintained by increasing the rubber level.

  Example 8 shows that a transparent gel can be prepared according to the present invention. In this case, it is important to maintain the level of a given calcium-sequestering salt below its solubility limit or slightly above its limit, and therefore various salt combinations are used. This example also shows that the polyphosphate can be used in combination with a carboxylate calcium-metal sequestering agent.

  Example 9 shows that even if all the silica is excluded from the formulation, good cleaning can be maintained from the carboxylate calcium-sequestering agent.

  Example 10 shows that the formulations of the present invention can contain low levels of abrasive silica. It can be seen that when the final RDA value is 30 or less, the remarkable cleaning efficiency of the present invention is maintained.

  Example 11 shows a low viscosity liquid toothpaste formulation.

Example 12 shows a formulation comprising a zwitterionic surfactant, which can be used to minimize irritation that can occur in oral tissues.

  Example 13 is a formulation of the present invention comprising a therapeutic amount of potassium nitrate that relieves hypersensitive tooth pain.

  Example 14 is an anti-gingivitis preparation of the present invention containing Triclosan.

  Example 15 is a formulation of the present invention designed to achieve highly effective cavity prevention and includes 2,500 ppm fluoride, xylitol and casein phosphopeptide.

  Example 16 is a formulation of the present invention comprising an active enzyme to inhibit dental plaque and maximizes the stability of biological molecules by using a nonionic surfactant.

Example 17 is a formulation of the present invention suitable for dispensing from a pressurized aerosol container.

  The RDA of the 14% Zeodent 113 abrasive silica formulation shown in Table 4 was tested. The RDA value is higher than that of the formulation of the present invention.

Cleaning effect and abrasiveness test The cleaning effect of the formulation described in Example 1 was tested. Using the method of Layer et al., This formulation was tested in comparison to a standard abrasive-containing control toothpaste paste formulation (see Table 1), with water as the negative control. The formulation was also sent to Indiana University, Institute for Oral Health for RDA testing. The values for soil removal and abrasiveness are shown in Table 5 below.

  As can be seen from Table 5, the abrasiveness of the formulation according to Example 1 of the present invention was very low (RDA = 9.99). The abrasiveness of the control paste was within the expected range for this type of formulation. However, the cleaning value of the prototype formulation was 115.5 of the abrasive-containing control, revealing a very effective cleaning performance. The table also shows that brushing with water does not remove dirt from this substrate.

Claims (10)

  A dentifrice composition comprising a soluble calcium sequestering agent that is not an oxidizing agent, the composition comprising an RDA value of 30 or less and an IVSR value of 50 or more (as compared to a control), and an oral acceptable The dentifrice having a vehicle, wherein the calcium sequestering agent is present in a proportion of 1 to 20% by weight of the composition and the abrasive is present in a proportion of 0 to 5% by weight of the composition Composition.   The dentifrice composition according to claim 1, wherein the RDA value is 20 or less and the IVSR value is up to 250.   Dentifrice composition according to claim 2, wherein the calcium sequestering agent is present in an amount of 2 to 15% by weight of the composition.   The dentifrice composition according to claim 3, wherein the soluble calcium sequestering agent is a calcium chelating agent.   The dentifrice composition according to claim 4, wherein the calcium chelating agent is a polyphosphate or a pyrophosphate.   The dentifrice composition according to claim 5, wherein the pyrophosphate is pentasodium tripolyphosphate.   The dentifrice composition according to claim 6, wherein 0% by weight of an abrasive is present in the composition.   The IVSR values are measured in comparison to a control dentifrice formulation containing 14% Zeodent 113 abrasive silica in a normal base material containing water, sorbitol, glycerin, PEG, flavor, SLS, sodium saccharin, xantham gum and sodium fluoride. The dentifrice composition according to claim 7.   A dentifrice composition according to any one of the preceding claims, used for treating natural teeth or dentures.   Dentifrice composition according to any one of the preceding claims, in the form of a viscous, extrudable fluid that can be provided in a collapsible container.